Cell Therapeutics Inc. began its first Phase III trial of Xyotax, a program expected to be followed by other studies of the drug with shorter timelines.

"This is a front-line treatment study for advanced ovarian cancer patients," said James Bianco, president and CEO of Cell Therapeutics. "This is the only one in ovarian. We have studies planned in lung that will start up shortly as well."

The study is a non-inferiority trial that will involve about 964 patients and examine Xyotax in combination with carboplatin vs. Taxol combined with carboplatin. The primary endpoint is progression-free survival, with secondary endpoints of response rates and overall survival. The study is designed to demonstrate Xyotax's superior side effect profile to the Taxol arm of the study. However, although this is the first Phase III trial for Xyotax, it is scheduled to take the most time and probably won't support the product's first NDA.

"This has the longest timeline that we have set," Bianco told BioWorld Today. "We think it will have 18 months of enrollment and 15 months of follow-up. The NDA probably won't get filed until 2005."

That puts ovarian cancer patients as the third population that might benefit from Xyotax approval, Bianco said. If the company is able to begin in a timely fashion a Phase III trial in non-small-cell lung cancer patients, a filing could come in the second half of 2004. But look for the first NDA filing for Xyotax to come earlier in 2004 in a still-undisclosed indication, he said.

"A second-line lung study should begin at the end of this summer in patients who have failed front-line platinum-based regimens," Bianco said. "We have a target for the second half of [2004]; we'd like to find a target for [filing in early 2004]. We think we may have a population."

Cell Therapeutics is in discussions with the FDA concerning that indication, and the trial could begin in September, Bianco said.

The product is in Phase I studies in advanced solid tumors in Europe and Phase II studies in colorectal cancer.

Xyotax links paclitaxel to a biodegradable polyglutamate polymer. The polymer is optimally sized, Bianco said, and is trapped in the porous blood vessels in tumors. Because tumor blood vessels are structured differently than vessels in normal tissue, more paclitaxel is delivered to the tumor, leaving less in the body.

With Xyotax, "you have very low levels of free paclitaxel in the bloodstream," Bianco said. "It is active in the [tumor] tissue but not in the bloodstream. Because of that, we see no significant hair loss. You don't see people going bald on this drug. With Taxol, they tell you, Shave your head, because in two weeks it will all fall out.'"

Although that is the most visible sign of Xyotax's potential improved side effect profile over Taxol, the Phase II data also show that there is no anemia or severe neuropathy, Bianco said.

"There's a lot of buzz in the ovarian community," he said. "If you can treat [ovarian cancer] effectively without the side effects, it's an important treatment."

Seattle-based Cell Therapeutics plans to market the drug itself in the U.S., using the infrastructure it built to sell its marketed product, Trisenox. In Japan, Xyotax is partnered with Chugai Pharmaceutical Co. Ltd., of Tokyo, in a deal signed in October and worth up to $73 million. Cell Therapeutics has been in discussions for a partner in Europe. (See BioWorld Today, Oct. 23, 2001.)

Trisenox, Cell Therapeutics' product that was approved to treat acute promyelocytic leukemia patients whose disease has recurred after initial therapy, brought the company $2.4 million in net product sales in the second quarter. That represented a 60 percent increase over 2001's second quarter, and Bianco said the third quarter "is shaping up really well." Overall, the company had revenues of about $2.8 million for the second quarter and posted a net loss of about $26.5 million. As of June 30, it had $195.9 million in cash, cash equivalents, securities available for sale and interest receivable.

Besides Trisenox, the company has PG-CPT finishing its Phase I work now. Bianco said the product should begin Phase II studies "probably at the end of the year." The drug is Cell Therapeutics' polyglutamate polymer attached to camptothecin.

The initiation of the Xyotax Phase III trial says something about Cell Therapeutics' ability to develop products, Bianco said.

"We started Phase I in 2000 and we are starting Phase III in 2002, with a lot of Phase II data," Bianco said. "This has been a rapid development path and that has been our commitment - to get products as quickly as we can to market."

Cell Therapeutics' stock (NASDAQ:CTIC) rose 36 cents Tuesday, or 11.5 percent, to close at $3.49.

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